Male gender is a risk factor for the development of central apnea. This assertion is supported by epidemiologic as well as empiric evidence. Epidemiologic studies demonstrate paucity of CSA in premenopausal women (34) and in patients with CHF and Cheyne-Stokes respiration (CSR) (35).

The hypocapnic apneic threshold during NREM sleep is higher in men relative to women. Using nasal mechanical ventilation, Zhou et al. (36) have shown that the apneic threshold was -3.5 mmHg versus -4.7 mmHg below eupneic breathing in men and women, respectively. In addition, no difference was noted in women in the luteal versus the follicular phase of the menstrual cycle. Thus, the gender difference was likely due to male sex hormones rather than progesterone.

The role of male sex hormones was confirmed in studies that manipulated the level of testosterone in men and women. Zhou et al. (27) have shown the administration of testosterone to healthy premenopausal women for 12 days resulted in an elevation of the apneic threshold and a diminution in the magnitude of hypocapnia required for induction of central apnea during NREM sleep. In fact, the apneic threshold in women after testosterone administration was identical to the apneic threshold in men (37). Conversely, suppression of testosterone with administration of long-acting gonadotropin-releasing hormone decreased the partial pressure of end-tidal carbon dioxide PETCO2 that demarcates the apneic threshold (38). Thus, male sex hormones seem to play a critical role in the susceptibility to develop central apnea during NREM sleep.

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